Puerarin, isolated from Kudzu root (Willd.), attenuates hepatocellular cytotoxicity and regulates the GSK-3β/NF-κB pathway for exerting the hepatoprotection against chronic alcohol-induced liver injury in rats

Int Immunopharmacol. 2013 Sep;17(1):71-8. doi: 10.1016/j.intimp.2013.05.023. Epub 2013 Jun 7.

Abstract

Puerarin (PR) has been utilized as a phytomedicine to managing liver disease in China. Thus, this study aimed to evaluate the potential PR-mediated hepatoprotective role against chronic alcohol-induced liver injury in rats. The results indicated that serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and pro-inflammatory cytokines were significantly reduced following PR treatment, while the albumin (ALB) level was increased. Meanwhile, intrahepatic contents of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) were elevated. Pathological examination showed that alcohol-lesioned hepatocytes were mitigated through the PR treatment. In addition, the endogenous levels of glycogen synthase kinase-3β (GSK-3β) at the protein level and β-catenin expression at the mRNA level were notably down-regulated, whereas the tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B (NF-κB) proteins in the liver tissue were effectively decreased following the PR treatment. Together, these findings demonstrate that PR mediates hepatoprotection against alcohol-induced liver injury. The mechanisms underlying the cytoprotective effects of PR are associated with inhibiting immunotoxicity in hepatocytes and regulating the GSK-3β/NF-κB pathway, thereby maintaining metabolic homeostasis in the liver tissue.

Keywords: Alcohol; GSK-3β/NF-κB pathway; Immunotoxicity; Liver injury; Puerarin.

MeSH terms

  • Animals
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Hepatitis, Alcoholic / drug therapy*
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Male
  • Molecular Structure
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Plant Roots / chemistry*
  • Pueraria / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Isoflavones
  • NF-kappa B
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3
  • puerarin